Health Information

ACTH
ACTH regulate glucocorticoids
Basal release.
Response to stress.
ACTH also increase sensitivity to the further ACTH – takes sometime to restore ‘normal function’.
Important after withdrawal of glucocorticoids treatment.

There is a diurnal rhythm in ACTH and glucocorticoids level – more between 4 am to 10 am.
Rate of ACTH secretion determined by
Neural stimuli through hypothalamus
Feed back inhibition from glucocorticoids in blood.

Stress and ACTH
ACTH secretion in stress totally under control of hypothalamus and CRH.
Paraventricular nuclei get afferents from different places in the brain.
Summary
Hormones from adrenal cortex.
ACTH effect on adrenal cortex.
Angiotensin II effect on adrenal cortex.
Cortisol transport, corticosteroid-binding globulin, function and metabolism.
Glucocorticoids as a stress hormone.
Anti-inflammation effects of Glucocorticoids.

suppress the cell-mediated immunity by inhibiting genes that code for the cytokines.
suppress the humoral immunity causing B cells to express smaller amounts of IL-2 and of IL-2 receptors.
Use for treating asthma, inflammatory skin diseases, allergy, etc.
Need to be careful about those with infections – infection can be aggravate.
Anti-inflammation & glucocorticoids
Sudden withdrawal can be dangerous since low ACTH secretion and pituitary unable to secrete normal amount for sometime.
Local administration is better and prevent most side effects.

secreted in higher levels response to stress.
ACTH secrete with stress.
Have short terms positive effects:
A quick burst of energy for survival reasons
Heightened memory functions
A burst of increased immunity
Lower sensitivity to pain
Helps maintain homeostasis in the body
Glucocorticoids as the stress hormone
Have long term (chronic) negative effects
impaired cognitive performance
Suppressed thyroid function
Blood sugar imbalances such as hyperglycemia
Decreased bone density
Decrease in muscle tissue
Higher blood pressure
Lowered immunity and inflammatory responses in the body, as well as other health consequences
Increased abdominal fat, which is associated with a greater amount of health problems than fat deposited in other areas of the body.

Increase and maintain normal blood glucose.
Stimulation of gluconeogenesis in the liver.
Mobilization of amino acids from extrahepatic tissues.
Inhibition of glucose uptake in muscle and adipose tissue.
Stimulation of fat breakdown in adipose tissue.
Certain permissive action
Need for glucagon exert calorigenic effects.
Need for calorigenic, lipolytic, pressor reponses and brochodilation effects of catecholamines.
Fetal development - maturation of the lung and production of the surfactant necessary.
Changes in blood.
Some white cells increase and some decrease.
Increase RBC and platelets.
Potent anti-inflammatory and immunosuppressive effects.

Bind in circulation to corticosteroid-binding globulin (CBG) (Transcortin)
Also some bind to albumin
Corticosterone also similarly bound but lesser degree.
Bound forms are physiologically not active. But act as a reservoir to keep free form available.

CBG synthesis in liver –
Production increase by oestrogen.
Increase in pregnancy.
Decrease in cirrhosis, nephrosis, multiple myeloma.
If CBG increase, free cortisol decrease temporarily then compensated with increase ACTH.

Cortisol metabolized in the liver.
Conjugated to glucuronic acid by glucuronyl transferease system.
Cortisone (medical usage !) form in the liver but very little enter to circulation.
Conjugated form is water soluble and excrete with urine.
Cortisol
15% secreted cortisol is excrete with stool – enterohepatic circulation
Corticosterone also have similarly metabolism.
In stress, liver inactivation decrease and help to increase cortisol level.

Facilitate formation of 18-hydroxycorticosterone and then aldosterone.
The renin-angiotensin-aldosterone system.
Main drive of aldosterone.

Mineralocorticods – effect of Na+ and K+ excretion mainly.
Glucocorticoids – effect on glucose and protein metabolism mainly.
Androgens – masculinizing effect mainly.

Hormones from adrenal cortex
Mineralocorticods – aldosterone, deoxycorticosterone.
Deoxycorticosterone secrete equal amount of aldosterone, but has 3% effect of aldosterone.
Glucocorticoids – cortisol, corticosterone.
Cortisone is a active form, but not secrete.
Androgens – dehydroepiandrosterone, adrostenedione, testosterone.
Dehydroepiandrosterone is conjugated with sulfate. (contrary to all other steroids are free form)
Action of ACTH
Tropic hormone for adrenal cortex.
Secreted from the anterior pituitary in response to corticotropin-releasing hormone from the hypothalamus.
Facilitate conversion of cholesterol to pregnenolone in adrenaocortical cells.
Stimulates secretion of glucocorticoids.
Has little control over secretion of aldosterone.